Adult acute leukaemia--a suitable case for treatment?

'NTRODUCTION Many physicians have, in the past, doubted the va ue of aggressive treatment for acute leukaemia in iqU'tS^his view has had much justification. Between 19r8 (TiveV< 1954) and 1966 (M.R.C. Working Party, ?6) the average survival had remained constant at around 70 days, despite the fact that antibiotics and ??d transfusion had been supplemented by cytotoxic j"u9s capable of inducing remission in over 80% of

19r8 (TiveV< 1954)  ). By 1965 Burchenal was already talking of e Prospect of cure in childhood acute leukaemia and sited 53 patients who had survived longer than five ^ears (Burchenal et al. 1965). However, he could find n V six adults in whom there was even a possibility of cure.
Skipper's experiments on the transplanted murine ^ukaemia (Skipper et al., 1964) revealed an important erence between normal and abnormal cells that ^ u|d be used in treatment. Normal cells grow more P1 d1 y, ancj therefore, if a large number of normal and c norrnal cells are killed, the normal cells should re-beV8r *'rst' a"?wing a further course of treatment to 9iven. Successive courses of treatment would rethe numbers of leukaemic cells to levels that ism ^ '1anc"ec' by the body's own immune mechan-^xperimental treatment schedules based on this C|ple were quick to appear, and have been successln Prolonging life in patients treated at research n*res (Crowther et al., 1970). e set out to examine whether such heroic treatdi Sched"'es were applicable in the context of a str|ct general hospital. PaTIENTS and methods an e'9^teen month period 15 patients were five' te^ suffering from acute leukaemia. There were to rt"13'05 and ten ^emales and age range was 22 -with a mean age of 50. ^etails are given in Table I Cytotoxic drugs used (Table II). Patients with acute myeloblastic leukaemia and erythro-leukaemia were treated with cytosine arabinoside 2 mg/kg by intravenous injection daily for five days, with daunorubicin 1.5 mg/kg by fast intravenous infusion on day 1. This was repeated every 10 days until blast cells disappeared from the peripheral blood and bone marrow. After remission, maintenance treatment was given every 6 weeks, consisting of cytosine arabinoside and daunorubicin as above, alternating with cytosine arabinoside or 6-thioguanine 2 mg/kg orally for 5 days. In the event of relapse, methotrexate, 6-mercaptopurine or cyclophosphamide were added to these schedules.
One patienlt with acute lymphoblastic leukaemia was treated by the technique described by Aur et al. (1971).
Marrow depression was anticipated and treated in the following manner.
Anaemia was treated when symptomatic by the transfusion of packed red cells.
Thrombocytopenia was treated initially only when accompanied by signs of a haemorrhagic diathesis, such as bruising, purpura or frank bleeding. At a later stage, when platelets for transfusion became more easily available, we treated when the platelet count fell below 20,000//zl. Platelet concentrates from 4-6 donors were injected intravenously daily as necessary.
Neutropenia was treated expectantly.
When the neutrophil polymorph count fell below 500/^tl we instituted reversed barrier nursing in cubicles off the general ward. Infections were treated with appropriate antibiotic after identification of the organism, and after consultation with the microbiologist, Dr. D. S. Reeves. Occasionally it was necessary to start treatment before an organism had been identified, and a suitable combination of antibiotics was used, again on the advice of Dr. Reeves. We did not use prophylactic antibiotics, nor did we attempt to sterilise the patient's bowel or his food.

RESULTS
Of the fifteen patients, six achieved a complete remission (normal blood count and normal bone marrow with a return to normal life). Two   remissions, with return to normal life, and disappearance of blasts from peripheral blood and bone marrow, but accompanied by a degree of marrow hypoplasia, reflected in neutropenia and thrombocytopenia in the Peripheral blood. There were four deaths before the completion of the first course of treatment. In three cases death resulted from ov:'"whelming infection that had been present at diagnosis, and in the fourth a pontine haemorrhage was associated with a pre-existing thrombocytopenia. There were three treatment deaths during the phase of marrow aplasia, all from haemorrhage associated with thrombocytopenia. These results are summarised in ,^evere hypoplasia lasted between one and aafi 'n those achieving a remission, with an aver-9e two weeks. and , ern'3. All patients were anaemic at presentation came more so on treatment. Apart from two early deaths all required blood transfusion. A total of 165 units of packed red cells were transfused, an average of 11 units per patient. One patient developed a red cell isoantibody following blood transfusion. All patients achieving a remission were able to maintain a normal haemoglobin.
Thrombocytopenia. The platelet count at presentation is given in Table I. Those who were not already thrombocytopenic rapidly became so on treatment. A total of 200 units of platelet concentrate were given, the majority prophylactically because of a low platelet count.
Two patients became refractory to platelets and died of haemorrhage, one intracerebral, and the other retroperitoneal. A further patient died of haemorrhage into the pericardial cavity despite the fact that donor platelets had raised his count to 34,000/^1. There was one other case of severe haemorrhage, this time into middle and inner ear, which was arrested after platelet transfusion. The patient survived for nearly nine months after the episode, and despite being totally deaf she fitted well as an aged grandmother into a household which luckily made little use of verbal communication.
Neutropenia. This was also a regular feature in those who survived the first course of treatment, and all of these patients were barrier nursed at some stage of their treatment. Fifteen patients spent 42  All the patients surviving the first course of treatment suffered infective complications, though most of them were minor. The mouth was the most common site. There were six episodes of gingival or peridontal infection, two of tonsilitis, two of labial herpes simplex, two of oral candidiasis, and one of parotitis.
Two of the infective episodes occurred after medical interference; an infected infusion site led to a staphylococcal septicaemia, and a staphylococcal abscess occurred at the site of an intramuscular injection.
There were two cases of bronchopneumonia, and a middle ear infection. All of the other bacterial infections began in the skin. A staphylococcal septicaemia started life as a pustule on a finger, and a patient presenting with perineal ulceration developed perineal cellulitis.
There were in addition two episodes of presumed viral infection which were asymptomatic and selfresolving. The patients presented with neutropenia, thrombocytopenia and an atypical mononucleosis while safely in remission. Bone marrow examination showed an infiltration with atypical mononuclear cells, but no sign of relapse. Tests for infectious mononucleosis, toxoplasmosis and cytomegalovirus all proved negative.
There were no deaths from infection in patients made neutropenic by the treatment.
Depression. None of the patients enjoyed being isolated in cubicles and four complained of depression. In addition, one patient suffered a severe depressive psychosis which required psychiatric help.
Neurological. None of the patients receiving vincristine developed a peripheral neuropathy, but the patient who had cranio-spinal irradiation developed 3 radiculitis which interfered with walking. This was slow to resolve but the patient (10) is now leading * normal life.
Other drug reactions. One patient had an urticarial reaction to flucloxacillin, and another suffered acute renal failure after being treated with the combination1 of frusemide, gentamicin and cephaloridine. Both of these patients made a complete recovery. Most patients receiving cytosine arabinoside complained of transien' nausea. One patient had T wave inversion in her ECC after daunorubicin, but this was asymptomatic.
Quality of life in remission. Those patients achievinf a remission were able to return to their normal occu pation if they desired. Ideally the only medical demand' on their time were weekly venepunctures, and a week end admission every six weeks for bone marrow ex amination, and daunorubicin infusion. Cytosine ara binoside may be given subcutaneously, and patients may be trained to inject themselves as diabetics do. Some patients elected not to return to their olc routine but to enjoy an extended holiday. One patien1 devoted her last six months to raising money fo1 cancer research. On the other hand, one patient has been running his own business successfully for over 1 year since his illness.
All the patients felt subjectively well. Indeed, somc of them experienced difficulty in getting their familie-' and friends to reconcile their apparent well-being wit'' their sinister diagnosis. ?rking Party, 1971). The treatment itself is hazard-0US' and it is necessary Ito assess whether it is approbate to introduce it into a district general hospital. study of children with acute lymphoblastic leukaemia shows that results are better when the patients are treated in a specialised centre.
Published series showing good results are often small and selected. There is usually an age limit above w 'ch treatment is not offered, and in some series the m?re malignant variants such as erythroleukaemia and onocytic leukaemia are excluded. Many series com-?h'S? mainly referred cases, and consequently exclude ose patients whose clinical condition is so poor on lagnosis as to preclude referral. Ur saries, though small, is unselected. Neverthess, our remission rate of 55% compares favourably "?h the best yet reported (Crowther et al. 1970